Aryl-alkenones



March 16, 1965 M, G, J, BEETS ETAL 3,173,955

ARYL-ALKENONES Filed Aug. 1, 1962 2 Sheets-Sheet l FIGA FRE UENCY ma squame manina www umu una (cugopospo I so 80o fao m leo UG UJ Y u z gm E nm gne Y 1 z s l'. s e 7 a s 1o n 12 m 5 WAVELENGTH (MICRONS) FREQUENCY (cw) Fl G .2 1,0m wqm 1...@ n Q00 .n 7

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ARYL-ALKENONES Filed Aug. l, 1962 2 Sheets-Sheet 2 FREQUENCY Lcw) FG'S w sohm im en nq ik L was Q0 Bw E 7m 6.5 00

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i 1 B 9 10 4I I2 wAvELENGTH (MlRoNs) FREQUENCY (0'4") F165 um seaonsos hummm noe mnogwasaapgg 'roo gg m 6 7 s 9 so n 12 wAvELENGTH (Ml cnous) nited States Patent 3,173,955 ARYL-ALKENGNES Muns G. I. Beets, Wilhelmina Meer-burg, and Wilhelmus .L Wiegers, Hilversum, Netherlands, assignors to International Flavors d; Fragrances LEF. (Nederland) N V., Zaandam, Provincialeweg, Netherlands Filed Aug. 1, 1962, Ser. No. 4,063 Claims priority, application Great Britain, Ang. 9, 1961, 28,7411/ 61 7 Claims. (Cl. 260-590) We have discovered that unsaturated aryl aliphatic ketones of the general structure I in which Ar is phenyl or methylphenyl and in which R1 and R2 are hydrogen or lower alkyl with a total number of carbon atoms not exceeding two, are outstanding perfumes.

Especially in the case where Ar is phenyl, R1 is methyl and R2 is hydrogen, the compound (il) represents a new material of extraordinary intensive and valuable odour.

on, o @-o-onrfi-o-:C n,

H3 CH3 UI) Although 2,5-dimethyl5-phenyl-hexen-l-one-3 (Il) has a strong interesting and definite odour, it is easy to blend into speciiic and widely Varying types of perfumes in relatively large amounts. It shows an excellent tenacity and can be used in perfume composition as well as in articles in which such Compositions are used such as soaps, cosmetics, powders, aerosols, creams, lotions and the like.

The same holds good for other representatives of this group of which the compounds III-VIII, all with excellent properties, are mentioned as examples.

We have also discovered that compounds according to this invention are useful as avouring materials.

Products according to the present invention may be obtained in several ways of which the following are mentioned as examples.

(A) Elimination of HX from compounds of the general type IX, in which Ar, R1 and R2 have the meaning arrasa? Patented Mar. i6, 1965 und' 2 mentioned above and in which X can represent hydroxyl, halogen or an ester group.

| H3 Ri Rn (IX) This can be realized either by direct dehydration oi the carbinol (XZOH) under the inuence of catalysts such as sulphuric acid, toluene sulphonic acid, acid salts, boric anhydride, boric acid or by pyro-lysis of the corresponding esters such as acetates, propionates, stearates, metaborates, xanthates or sulphites.

Compounds of type 1X may be obtained in several ways of which the following examples are mentioned.

(1) Friedel Crafts condensation of aromatic hydrocarbons with tetra alkyl tetrahydrofuranone (see H. A. Bruson, I.A.C.S. 80, 3636 (1958)) O CH3 0 OH ma! L aannam O H3 H3 (2) Condensation 4of neophylmagnesiumhalides with eyan-ohydrins of ketones or aldehydes in which the hydroxyl group is protected, eig. by means of a tetrahydropyranyl group CH3 N R2 of type X may be obtained in several Ways of which the following examples are mentioned.

(l) Mannich reaction of ketones with aldehydes and amines CH3 O Ar--CHg-(li--CHZ -l- HC=O -I- HN/ H3 Rx Ri CH3 0 Ar-(lJ-CHg-(Hl-CH-CH-N/ H3 112.1 Ilia (2) Aldol condensation of ketones with aldehydes.

(C.) Oxidation or' catalytic dehydrogenation of unsatu' rated alcohols of type XI in which Ar, R1 and R2 have the meaning, mentioned above.

(D) Dehydration of ketoalcohols of the general type XII under conditions which favour rearrangement CH3 OH 0 .Ar-([J-CHz-- v lli VHiRz H3 (XII) When a carbinol of type XII is dehydrated catalytically Y in the presence of acid a rearrangement takes place which may be formulated as follows That the structural criteria mentioned above do indeed delimitate the scope of the invention is demonstrated by the following considerations.

(lst) The introductionl of a methyl group in the aromatic nucleus causes a slight decrease in the intensity of the odour but the compounds III and IV still retain the powerful rose-type odour of II, although shifted somewhat towards the woody type.

When, however, anV ethyl group is introduced into the phenyl group, the odour weakens considerably. XIII (B.P.3 mm, 122; 111,20 1.5158) as well as XIV (B.P.3 mm 119; nD20 1.5151) have a characteristic but rather weak odour.

(2nd) Replacement of one of the gemini methyl groups by ethyl XV (B.P.3 mm 116; nD20 1.5170) leads to a considerable decrease of the odour.

(3d) The compound XVI (B.P.3 mm 130; D20 1.5157), obtained by aldol condensation of isobutyric aldehyde with 2-methyl-2.phenylpentanone-4 has a very weak odour.

(4th) 2,5 dimethyl 2 phenyl hexanone 4 (XVII; B.P.3 mm. 100; m32 1.5001; 142 01.9496), obtained by hydrogenation of II, possesses a fairly weak, uncharacteristie odour.

H3 C Ha (XIV) CHZCHg O H3 Ha (XV) CH3 CH3 CH3 Ha (XVI) CH3 o' @eMail-Caca.

on@ CH3 (Xvny The'foll'owing'exariiples may illustrate the preparationi of compounds according to`thepresent invention.

('1 2,5-dimethyl-5-ph'eriy l-hexene-I lona-3 1106 g`. (0.40 ni-ole) of 2 -acetoxy-2,5dimethyl5-phenylhexanfon-S (B.P.3 mm.. 134; 11520 1.4993) were'intro--- duced at a pressure of to 110 (nitrogen atmos-l phere) into a reactor consisting" of a' glass tube packedl with glass helices at 350 -to 400 C. during4 hours. The.: crudegreactiori product was washed to neutral reaction;` and fractionated through a l-plate Vigreux column... The yield was 75 to 80%. All fractions showed a con-:- stant boiling point and'refractive index and were pure on gas chromatography. HD2 1.5222; B.P.3 mm 110 C.;;; colourless liquid.

The product is stabilized with a small amount of one" of the usual Vinhibitors such as hydroquinone. In unsta-- =bilized formiit'sh'ows a tendency to dimerize. However, upon heating (distillation) the dimer dissociates easily: and the monomer can always be recovered in nearly quan.- titative yield. g

Melting point semicarbazncine':` l5V6.4-157.0. The inf fnared spectrum is shown i.`n` FIGURE 1 of the acoomf panying drawing.

2,5 dimethyl 5 (methyl phenyl) hexanol 2 one-3 (B.P.3 mm. 132; nD2 15092-45098; mixture off rnand p-isomers) was obtained by condensation of tolufene with tetramethyl-tetrahydrofuranone according to Bruson.

The corresponding acetate (B.P.3 mm. 145 111320? 1.4992) was pyrolyzed according to Example 1.

A mixture of about 72% para and 28% meta-isomers; of the desired product (B.P.3 mm 115; nD20 1.52002: i420 0.97015) was obtained in 70% yield. Colourless-` liquid with strong odour, the rose character of which is shifted somewhat Ytowards the woody note. The two isomers could be separated by gas liquid partition chroma* tography (G.L.P.C.). 2,5dimethyl-5-(4methylpheny1)hexene1one3; nD2 1.5196 p-isomer; corresponding m-isomer; nD2 1.51202. The I R. spectra of these com.-4 pounds are shown in FIGURES 2 and 3.

In a 250 ml. distillation ask, ritted for continuous: azeotropic water separation were placed55 g. of xylene,. 5.5 g. of toluene-sulphonic acid and 55 g. (0.25 mole) of 2,5-dimethy1-S-phenyl-hexanol-Z-one-S (B.P.3 mm. 125;` 111320 1.5100). The solution was refluxed for 30 min.. during which Iperiod nearly the theoretical amount of" water was separated. The xylene solution was washed"` and fractionated. B.P.2,5 mm, 103; 111320 1.5220. The` product contained only traces of 1,1,4,4tetramethyl-tetralone (M P. 74.8-75.3).

(4) 2,5-dimethyl-5-phenyl-hexene-1-one-3 110 g. (0.5 mole) of 2,5dimethyl-5-phenyl-hexanol- 2-one-3 were introduced into a reactor consisting of a glass-tube packed with 17.5 g. of boric anhydide on 45.5 g. of pumice in nitrogen atmosphere at 100-110 mm. and at 260 C. in 21/2 hours. Since the conversion was incomplete (checked by G.L.P.C.) the treatment was repeated twice until the G.L.P.C. analysis of the crude product showed the absence of starting material.

The crude reaction product was washed and fractionated through a 16-plate YVigreux column. The yield was 65% of theory. 111320 15220-15223. B.P.2 5 mmh -107 C.

110 g. (0.5 mole) of 2,S-diinethyl-5-pheny1-hexanol- 2-one-3 .were heated with 34.5 g. (0.55 mole) of boric acid and 0.11 g. hydroquinone to 140 at 15 mm. While Water was removed by distillation and kept at 140 for 45 minutes. The reaction product was liash distilled and fractionated in vacuo. 37% of theory of the desired product were obtained While 34% of starting material Was recovered.

(6) 2,5 dimethyl-5 -phenyl-h exene-I -one-3 25 g. (0.114 mole) of 2,5-dimethyl-S-phenyl-hexanol- 2-one-3 were slowly distilled in the presence of 4.4 g. (0.063 mole) of boric anhydride through a 16-plate Vigreux column at 13.5 mm. The reaction product was refractionated and 2,5-dimethyLS-phenyl-hexene-1-one-3 (B.P.1 5 mm 1005"; nnm 15219-15221) was obtained in a yield of 58%.

(7) 5-methyl-Z-elhyl-S-pkenyl-hexeue-I-one-3 and 2,5- dimethyl-Z-phenyl-heptene-S-one-4 To a solution of 4 g. of gaseous hydrochloric acid in 400 g. of ether was added in 1 hour at 25-30 a mixture of 840 g. (10 moles) of dihydropyran and 792 g. (8.0 moles) of Z-cyano-butanol-Z (B.P.3 mm, 62; 111320 1.4140). A solution of 2 g. of gaseous hydrochloric acid in 200 g. of ether Was added and the mixture was allowed to stand overnight. The reaction product was stirred with a solution of 400 g. of potassium .carbonate in 600 g. of Water, Worked up and fractionated in vacuo. Yield of 2-tetrahydropyranyloxy-Z-cyanobutane 83 of the theory. B.P.3 mm 78, 1:1320 14432-14456.

A solution of neophylmagnesiumchloride was prepared from 228.4 g. (9.4 moles) of magnesium in 850 g. of dry ethyl-butylether and from 1516.5 g. (9.0 moles) of neophylchloride in 1516 g. of ethylbutylether in the usual Way.

At 35-45 a solution of 1134.6 g. (6.2 moles) of the tetrahydropyranylether obtained in the same amount of ethylbutylether was added in 11/2 hours.

Stirring Was continued at reflux temperature for 2 hours and 3000 g. of Water were added at reux temperature in 1 hour. 2160 g. (36 moles) of acetic acid and 1300 of 36% hydrochloric acid were added. After the addition of each the mixture was stirred for 1 hour at 40-50".

After having been worked up, the crude product was fractionated through a 16-plate Vigreux column.

(B.P.3 mm 132; nD20 1.5078; pure on G.L.P.C., crystallizes on standing) was converted into the acetic acid ester (B.P.3 mm, 145; HD2 1.4998, ester value 202.2 or 99.6%) in the usual way. Yield 96%.

The pyrolysis was carried out according to Example 1 at 450-470 at 190 mm. in nitrogen atmosphere. A mixture of two isomers was obtained in a ratio of 3:2 which could be separated by fractionation at 3 mm. through a l6-plate Vigreux column.

(a) 5-methyl2-ethyl5-phenyl-hexene-1-one-3; B.P.3 mm 119; nD2 1.5182; 142D 0.9694; LR. spectrum FIG. 5. (b) 2,5-dimethyl-2-phenyl-heptene-S-one-4; B.P.3 mm, 125; HD2 1.5280; i420 0.9785; I. R. spectrum FIG. 7.

The odour of the first mentioned compound has a strong rose-like character, shaded to a green, rue like quality, that of the latter is similar, but more green and twiggy.

(8) 2-metkyl-2-ph enyl-hexen-5-0ne-4 Z-tetrahydropyranyloxy-propionitrile (B.P.3 mm 70; 1:1320 1.4397-14450; mixture of diastereomers according to G.L.P.C.) was condensed with neophyl magnesiumchloride according to Example 7. The hydroxyketone (2 components on G.L.P.C.) was converted into the acetate which was pyrolyzed according to Example 1. The product of the pyrolysis contained about 25% of recovered acetate, about 10% of 2-methyl-Z-phenyl-hexene-5-one-4 (B.P.3 mm 103; HD2 1.5251; LR. spectrum FIG. 4) and 33% of Z-methyl2phenylhexene3-one-5 (B.P.3 mm, 114; 113320 1.5348).

(9) 2-methyl-Z-phenyl-heptene-S-one-4 2-tetrahydropyranyloxybutyronitrile, (B.P.3 mm. 83; HD2 1.4428-1.4451, mixture of 2 steroisomers according to G.L.P.C.) was condensed according to Example 7 with neophylmagnesiumchloride. The hydroxyketone obtained Was converted into the acetate which was pyrolyzed according to Example 1. Z-methyl-Z-phenyl-hepten-S-one- 4 was obtained as a colourless liquid with an intensive odour (B.P.3 mm 116, 111320 1.5270).

(l0) Z-methyl-Z-phenyl-hexene-5-0ne-4 880 g. (5.0 moles) of 2-rnethyl-2-pheny1-pentanche-4, 478.5 g. (5.5 moles) of morpholine, 1250 ml. of isopropanol, 573 g. (5.5 moles) of 35% hydrochloric acid and 217.5 g. (7.25 moles) of para formaldehyde were reuxed for 12 hours. The reaction product was diluted With 3000 g. of Water, the neutral parts, 58 g., were extracted with benzene and 600 g. of 25% ammoniumhydroxide solution was added to the aqueous solution. The aminoketone (1313 g., 113320 1.5233) was extracted with benzene and converted into the hydrochloric acid salt with an ethereal solution of hydrochloric acid. Melting point, after recrystallisation from acetone 1232-1240".

290 g. (0.93 mole) of the so obtained Mannich salt were heated at 3 mm. Decomposition started at 130. The crude distillate was dissolved in benzene, Washed and fractionated through a 16-plate `Jigreux column. 2-meth yl-2-phenyl-hexene-5-one-4 was obtained as a colourless liquid with an odour of the type of gcranyland citronellylesters. 13.17.02 mm, 68; 121320 1.5250, i420 0.9873. With phenylhydrazine a pyrazolin derivative of MP. S50-85.5 was obtained. A part from the desired product some 2- methyl-2-phenylpentanone, formed by retro Mannich reaction Was obtained.

The product was shown to be identical to that obtained according to the method described in Example 8.

2-methyl-2phenyl-heptanone4 was converted into the Mannich salt according to Example 10. After decomposition according to the same example the reaction product was fractionated through a 17plate Vigreux column.

5 methyl-Z-ethyl-5-phenyl-hexene1one3 (3.13.3 mm, 15; HD2 1.5180; c1420 0.9690) was obtained as a colourless liquid with a powerful odour of the rose type which has shifted towards green rue-like notes.

The product was shown to be identical with the cornpound obtained according to Example 7.

Neophylmagnesiumchloride, prepared in ethyl-butylether, was condensed with methacrolein at 0-10". The reaction-product was fractionated through a saddle column of 25 cm. at 3 mm. Yield of 2,5-dirnethyl5phenyl hexene-l-ol-3 60%; B.P.3 mm, 115; nDzO 1.5208, :142 0.9675. Some 2,5-dimethyl-5phenylhexanal (formed by 1,4 addition) was obtained as a byproduct.

51 g. (0.25 mole) of the pure unsaturated alcohol, 87 g. (1.0 mole) of manganese dioxide and 500 ml. of benzene were refluxed for 10 hours. 3.0 ml. of water were removed azeotropically during this period. Excess manganesedioxide was removed and Washed and the reaction product was distilled. Weight: 42 g. G.L.P.C. showed that it consists of of the desired ketone and 20% of unconverted alcohol. Fractionation in vacuo yielded pure 2,5 dimethyl-5phenylhexene1-one3, B.P.3 mm, 106, H1320 1.5221.

Neophylmagnesiumchloride was condensed in ethylbutylether with crotonic aldehyde. 2methyl2phenyl heptene--ol-4 was obtained in a yield of 60%. B.P.3 mm 116; nD20 1.5201; i420 0.9620. To a solution of 448.5 g. (2.2 moles) of the unsaturated alcohol obtained in 1100 ml. of acetone, a solution of 440 g.V (1.48 moles) of sodiumbichromate 2 aq. and 580 g. (5.68 moles) of concentrated sulphuric acid in 2200 ml. of Water were added in 2 hours at 0-5 C.

Stirring was continued for 1 hour at 5-10 and the reaction product was worked up.

387 g. of distillate (B.P.3 mm 11C-160; 111,20 1.5251), containing 81.4% of ketone were obtained and subjected to a boric ester separation. The ketone obtained was fractionated at 3 mm. through a 16-plate Vigreux column. Two products were obtained; 2-methyl-2-phenyl-heptene- 5-one-4 (main product; B.P.3 mm. 15-118; HD2" 1.5268- 1.5272, assay by oximation 99%) and 2-methyl-2-phenyl- `heptene-l-one- (by rearrangement; B.P.3 mm. 124; n/DZU 1.5280; d420 0.9731). The odour of the latter compound is far less interesting than that of the main product.

2-methyl2-phenylheptene-5-one-4 is a colourless liquid with strong odour reminescent of jasmin absolute and of rhum. The LR. spectrum is shown in FIG. 6.

(14) Z-methyl-Z- (methyl-phenyl) -heptene-5-0ne-4 Methyl-neophylmagnesiurnchloride was condensed with crotonic aldehyde and the unsaturated alcohol obtained Was oxidizde, according to Example 13.

The desired ketone was obtained as a colourless liquid; B.P.0 6 mm. 10ft-110; 111320 15250-15260. The odour is Vsuggestive of jasmin.

2-methyl-2-methylphenyl-heptene-4-one-6 (B.P.06 mm 11G-116; 111320 15260-15270; formed by rearrangement) was obtained as a byproduct. The odour is weak with a touch of lcediarwood. Y

(l5) 2,5 dimethyl-5 -plzenyl-hexene-I -0ne3 only the desired product and no starting material was obtained in the receiver. The reflux ratio Was reduced (1) Rose-type composition 40 parts phenyl ethyl alcohol 15 parts geraniol ex citronella oil 15 parts citronellol 20 parts 2,5-dimethyl-S-phenyl-heXen-1-one-3 5 parts oc-ionone Y.

5 parts hydroXy-dihydrocitronellal 100 parts Replacement of 2,S-dimethyl-S-phenyl-hexen-1V-one-3 by rhodinol gives a considerably lower odour quality.

(2) Jasmin-type composition parts (3) Violet-leaftype composition 40 parts 15 parts 2 parts 5 parts 3 parts 100 parts A comparison between the composition before and afterV the addition of the compound according to the invention shows that the latterVV smoothes the odour and gives it a true violetleaf effect. This effect is still stronger after 20 hours on the smelling strip.

(4) Jasmin-type compositionl 25 parts 5 parts 5 parts 5 parts 5 parts 20 parts 10 parts 2 parts 3 parts 20 parts of benzylacetate of benzylpropionate of linalool of linalylacetate of hydroXydihydrocitronellal of -arnylcinnarnc aldehyde of phenyl ethyl alcohol of ylang ylang oil of heliotropin of Z-methyI-Z-phenyl-heptene-5-one-4 100 parts Comparison of the composition before and after addition of the compound according to the invention shows that the latter imparts to the composition a smooth, sweet jasmin effect.

After 20 hours on the smelling strip the first mentioned composition has a rough odour Whereas` the latter shows a natural jasmin character.

(5) Nerol-type composition 25 parts of terpeneless petitgrain oil 5 parts of linalool 10 parts of linalyl acetate 1 part of methyl anthranilate 5 parts of geraniol Y 10 parts of phenyl ethyl alcohol 10 parts of terpeneless bergamotte oil 2 parts of bitter orange Voil 2 parts of methyl-pianaphthylketone 30 parts of 2,5dimethyl-2-phenyl-heptene-Sone4 100 parts TheY addition of the compound according to the invention has an extremely favourable effect, especially on the backnote of the composition.

All temperatures herein referred to are in C.

What We carn is:

2. 2,S-dmethyL5-phenylhexene1-one-3. 1. An aryl-elkenone having the formula 3. 2,5dmethy15(3methy1pheny1)-hexen-Lone-3. CH3 O 4. 2,5-dimethy1-5(4'methy1-pheny1)-hexen-l-one-S. Il 5. S-methyLZ-ethyl-S-phenyl-hexene-Lone-3. AP" CH2-C`C2CH 5 6. 2,5-dimethyl-fbpheny-heptene-5-0ne-4.

CH3 R1 Rz 7. An ary1-a1kenone 2-'nethy1-2-pheny1-hepne-S- in which Ar is selected from the group consisting of One-L phenyl and 3 and 4 methylphenyl, and in which R1 and R2 are selected from the group consisting of hydrogen, References Cmd m the me of this Patent methyl and ethyl, the total number of carbon atoms in 10 Rupe et al.: Helv. Chim. Acta, Vol. 17, pages 372-89 R1 and R2 not exceeding 2. (1934) (page 376 relied upon).

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTIGN Patent No. 3,173,955 March 16, 1965 Muus G. J. Beets et a1.

It is hereby certified` that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 1, line 32, for "composition" read compositions column 3, lines 26 to 33, for that portion of the formula reading;

'E2C read H2O column 6 line 51 for' "150 read 115O Column 7 line 19 ferns-1180" read 11s-1180 same @01min 7, 1111533 for "oxldizde" read oxidized Signed and sealed this 3rd day of August 1965.

(SEAL) Attest:

ERNEST W. SWDER EDWARD J. BRENNER Anesting Officer Commissioner of Patents 

1. AN ARYL-ALKENONE HAVING THE FORMULA 